BIODISTRIBUTION AND DOSIMETRIC STUDY IN MEDULLARY-THYROID CANCER XENOGRAFT USING BISPECIFIC ANTIBODY AND IODINE-125-LABELED BIVALENT HAPTEN

The purpose of this study was to evaluate biodistributions and absorbe d doses of anti-carcinoembryonic antigen (CEA)/anti-diethylenetriamine pentaacetic acid (DTPA)-indium (anti-DTPA-In) bispecific monoclonal a ntibody (BsMAb) F6-734 and I-125-labeled DTPA-indium dimer hapten (I-1 25-di-DTPA-In hapten) in athymic mice xenografted with human medullary thyroid cancer. Methods: Bispecific monoclonal antibodies F6-679 (ant i-CEA/antihistamine) and G7A5-734 (antimelanoma/anti-di-DTPA-In) were used as irrelevant BsMAbs. Athymic mice inoculated with TT medullary t hyroid cancer cells expressing CEA were administered BsMAbs F6-734, F6 -679 or G7A5-734 and then, 48 hr later, I-125-di-DTPA-In hapten. Iodin e-125-labeled F6 F(ab')(2) fragment was injected into other groups of mice. Biodistributions were examined at 30 min and 5, 24, 48 and 96 hr after injection of I-125-di-DTPA-In hapten or I-125-labeled F6 F(ab') ,. Results: In mice injected with BsMAb F6-734 and I-125-di-DTPA-In ha pten, tumor uptake was 9.1% +/- 2.1%, 8.7% +/- 3.5%, 8.0% +/- 2.3%, 5. 1% +/- 0.9% and 3.5% +/- 1.5% of the injected dose/g at 30 min and 5, 24, 48 and 96 hr, and tumor-to-blood, tumor-to-liver and tumor-to-kidn ey ratios were 37.0 +/- 12.5, 32.3 +/- 10.9 and 10.4 +/- 2.7 at 24 hr. Iodine-125-F6 F(ab')(2) fragment showed a tumor uptake of 7.39% injec ted dose/g and tumor-to-blood, tumor-to-liver and tumor-to-kidney rati os of 1.8 +/- 0.6, 7.3 +/- 2.9 and 3.6 +/- 1.6 at 24 hr. In mice injec ted with F6-679 or G7A5-734, tumor uptake and tumor-to-normal tissue r atios were much lower than in the mice injected with F6-734. These res ults were confirmed by autoradiographic studies that demonstrated clea r tumor-to-normal tissue contrast. Conclusion: This two-step targeting method seems very potent for the diagnosis and therapy of human medul lary thyroid cancer and other CEA-producing tumors because it combines high tumor uptake and low normal tissue background.